Bacterial RNA-free RNase P: Structural and functional characterization of multiple oligomeric forms of a minimal protein-only ribonuclease P.

tRNAs are typically transcribed with extended 5' and 3' ends that must be removed before they attain their active form. One of the first steps of tRNA processing in nearly every organism is the removal of the 5' leader sequence by ribonuclease P (RNase P). Here, we investigate a recently discovered class of RNase P enzymes, Homologs of Aquifex RNase P (HARPs). In contrast to other RNase Ps, HARPs consist only of a metallonuclease domain and lack the canonical substrate recognition domain essential in other classes of proteinaceous RNase P. We determined the cryo-EM structure of Aquifex aeolicus HARP (Aq880) and two crystal structures of Hydrogenobacter thermophilus HARP (Hth1307) to reveal that both enzymes form large ring-like assemblies: a dodecamer in Aq880 and a tetradecamer in Hth1307. In both oligomers, the enzyme active site is 42 Å away from a positively charged helical region, as seen in other protein-only RNase P enzymes, which likely serves to recognize and bind the elbow region of the pre-tRNA substrate. In addition, we use native mass spectrometry to confirm and characterize the previously unreported tetradecamer state. Notably, we find that multiple oligomeric states of Hth1307 are able to cleave pre-tRNAs. Furthermore, our single-turnover kinetic studies indicate that Hth1307 cleaves pre-tRNAs from multiple species with a preference for native substrates. These data provide a closer look at the nuanced similarities and differences in tRNA processing across disparate classes of RNase P.

Periodontal treatment associated with decreased diabetes mellitus-related treatment costs: An analysis of dental and medical claims data.

BACKGROUND: Diabetes mellitus (DM) and periodontal disease have a suggested bidirectional relationship. Researchers have reported decreases in DM-related health care costs after periodontal treatment. The authors examined the relationship between periodontal disease treatment and DM health care costs in commercial insurance and Medicaid claims data. METHODS: This study of IBM MarketScan commercial insurance and Medicaid databases included overall outpatient, inpatient, and drug costs for patients with DM. The authors examined associations between overall health care costs per patient in 2019 according to use of periodontal services from 2017 through 2018 using generalized linear modeling. The average treatment effect on treated was calculated by means of propensity score matching using a logistic model for periodontal treatment on covariates. RESULTS: For commercial insurance enrollees, periodontal treatment was associated with reduced overall health care costs of 12% compared with no treatment ($13,915 vs $15,739; average treatment effect on treated, -$2,498.20; 95% CI, -$3,057.21 to -$1,939.19; P < .001). In the Medicaid cohort, periodontal treatment was associated with a 14% decrease in costs compared with patients with DM without treatment ($14,796 vs $17,181; average treatment effect on treated, -$2,917.84; 95% CI, -$3,354.48 to -$2,480.76; P < .001). There were no significant differences in inpatient costs (commercial insurance) or drug costs (Medicaid). CONCLUSIONS: Undergoing periodontal treatment is associated with reduced overall and outpatient health care costs for patients with DM in Medicaid and commercial insurance claims data. There were no significant differences in inpatient costs for commercial insurance enrollees or in drug costs for Medicaid beneficiaries. PRACTICAL IMPLICATIONS: A healthy mouth can play a key role in DM management. Expanding Medicaid benefits to include comprehensive periodontal treatment has the potential to reduce health care costs for patients with DM.

Oral Cancer Prevalence, Mortality, and Costs in Medicaid and Commercial Insurance Claims Data.

BACKGROUND: This study compared prevalence, incidence, mortality rates, treatment costs, and risk factors for oral and oropharyngeal cancer (OC/OPC) between two large United States adult cohorts in 2012-2019. METHODS: Medicaid and commercial claims data came from the IBM Watson Health MarketScan Database. Logistic regression analyses estimated incidence and risk factors for OC/OPC. Mortality was calculated by merging deceased individuals' files with those of the existing cancer cohort. Summing costs of outpatient and inpatient services determined costs. RESULTS: Prevalence of OC/OPC in Medicaid enrollees decreased each year (129.8 cases per 100,000 enrollees in 2012 to 88.5 in 2019); commercial enrollees showed a lower, more stable prevalence (64.7 per 100,000 in 2012 and 2019). Incidence trended downward in both cohorts, with higher incidence in the Medicaid (51.4-37.6 cases per 100,000) than the commercial cohort (31.9-31.0 per 100,000). Mortality rates decreased for Medicaid enrollees during 2012-2014 but increased in the commercial cohort. OC/OPC treatment costs were higher for commercial enrollees by $8.6 million during 2016-2019. OC/OPC incidence was higher among adults who were older, male, and white; used tobacco or alcohol; or had prior human immunodeficiency virus/acquired immune deficiency syndrome diagnosis and lower among those who had seen a dentist the prior year. CONCLUSIONS: Medicaid enrollees experienced higher OC/OPC incidence, prevalence, and mortality compared with commercially insured adults. Having seen a dentist within the prior year was associated with a lower risk of OC/OPC diagnosis. IMPACT: Expanding Medicaid dental benefits may allow OC/OPC to be diagnosed at earlier stages through regular dental visits.

Comparison of two diphenyl polyenes as acid-sensitive additives during the biodegradation of a thermoset polyester polyurethane coating.

AIMS: Biochemical hydrolysis and chemical catalysis are involved in the successful biodegradation of polymers. In order to evaluate the potential separation between biochemical and chemical catalysis during the biodegradation process, we report the use of two diphenylpolyenes (DPPs), all trans-1,4-diphenylbutadiene (DPB) and all trans-1,6-diphenylhexatriene (DPH), as potential acid-sensitive indicators in polymers. METHODS AND RESULTS: 1,4-Diphenylbutadiene and DPH (0.1% w/w) were melt-cast successfully with poly(ethylene succinate) hexamethylene (PES-HM) polyurethane (thermoset polyester polyurethane) coatings above 80℃. When these two DPP/PES-HM coatings were exposed to a concentrated supernatant with significant esterase activity resulting from the growth of a recently isolated and identified strain of Tremellomycetes yeast (Naganishia albida 5307AI), the DPB coatings exhibited a measurable and reproducible localized decrease in the blue fluorescence emission in regions below where hydrolytic biodegradation was initiated in contrast with DPH blended coatings. The fluorescence changes observed in the biodegraded DPB coating were similar to exposing them to concentrated acids and not bases. CONCLUSIONS: Our experiments resulted in (1) a method to blend DPP additives into thermoset coatings, (2) the first report of the biodegradation of polyester polyurethane coating by N. albida, and (3) demonstration that hydrolytic supernatants from this strain generate acidic region within degrading polyester coatings using DPB as the indicator. SIGNIFICANCE AND IMPACT OF THE STUDY: Our experiments confirm that N. albida is an active polyester degrader and that DPB is a promising acid sensitive polymer coating additive.

Brain capillary pericytes exert a substantial but slow influence on blood flow.

The majority of the brain's vasculature is composed of intricate capillary networks lined by capillary pericytes. However, it remains unclear whether capillary pericytes influence blood flow. Using two-photon microscopy to observe and manipulate brain capillary pericytes in vivo, we find that their optogenetic stimulation decreases lumen diameter and blood flow, but with slower kinetics than similar stimulation of mural cells on upstream pial and precapillary arterioles. This slow vasoconstriction was inhibited by the clinically used vasodilator fasudil, a Rho-kinase inhibitor that blocks contractile machinery. Capillary pericytes were also slower to constrict back to baseline following hypercapnia-induced dilation, and slower to dilate towards baseline following optogenetically induced vasoconstriction. Optical ablation of single capillary pericytes led to sustained local dilation and a doubling of blood cell flux selectively in capillaries lacking pericyte contact. These data indicate that capillary pericytes contribute to basal blood flow resistance and slow modulation of blood flow throughout the brain.

Altered post-stroke propulsion is related to paretic swing phase kinematics.

BACKGROUND: Gait propulsion is often altered following a stroke, with clear effects on anterior progression. Changes in the pattern of propulsion could potentially also influence swing phase mechanics. The purpose of the present study was to investigate whether post-stroke variability in paretic propulsion magnitude or timing influence paretic swing phase kinematics. METHODS: 29 chronic stroke survivors participated in this study, walking on an instrumented treadmill at their self-selected and fastest-comfortable speeds. For each participant, we calculated several propulsion-related metrics derived from anteroposterior ground reaction force or from center of mass power, as well as knee flexion angle and circumduction displacement during the swing phase. We performed a series of linear mixed model analyses to determine whether the propulsion metrics for the paretic leg were related to paretic swing phase mechanics. FINDINGS: A subset of the stroke survivors exhibited unusual braking forces late in the paretic stance phase, when strong propulsion typically occurs among uninjured controls. Beyond the effects of walking speed or walking condition, these braking forces were significantly linked with altered paretic swing phase mechanics. Specifically, large braking impulses were associated with reduced paretic knee flexion (p = 0.039) and increased paretic circumduction (p = 0.023). INTERPRETATION: The present results suggest that braking forces late in stance are particularly indicative of deficits in the production of typical swing phase kinematics. This relationship suggests that therapies designed to address altered swing kinematics should also consider altered force generation in late stance, as these behaviors appear to be coupled.

Capturing Upper Limb Gross Motor Categories Using the Kinect® Sensor.

IMPORTANCE: Along with growth in telerehabilitation, a concurrent need has arisen for standardized methods of tele-evaluation. OBJECTIVE: To examine the feasibility of using the Kinect sensor in an objective, computerized clinical assessment of upper limb motor categories. DESIGN: We developed a computerized Mallet classification using the Kinect sensor. Accuracy of computer scoring was assessed on the basis of reference scores determined collaboratively by multiple evaluators from reviewing video recording of movements. In addition, using the reference score, we assessed the accuracy of the typical clinical procedure in which scores were determined immediately on the basis of visual observation. The accuracy of the computer scores was compared with that of the typical clinical procedure. SETTING: Research laboratory. PARTICIPANTS: Seven patients with stroke and 10 healthy adult participants. Healthy participants intentionally achieved predetermined scores. OUTCOMES AND MEASURES: Accuracy of the computer scores in comparison with accuracy of the typical clinical procedure (immediate visual assessment). RESULTS: The computerized assessment placed participants' upper limb movements in motor categories as accurately as did typical clinical procedures. CONCLUSIONS AND RELEVANCE: Computerized clinical assessment using the Kinect sensor promises to facilitate tele-evaluation and complement telehealth applications. WHAT THIS ARTICLE ADDS: Computerized clinical assessment can enable patients to conduct evaluations remotely in their homes without therapists present.

An alternative early childhood caries risk surveillance methodology for public policy and practice advancements.

OBJECTIVES: Early childhood caries (ECC) negatively impacts many child health outcomes and can lead to greater costs for medical and dental care as well as negatively impact future oral health wellness. ECC risk factors are rooted in many social determinants of health. Addressing ECC at the population-level is a national public health priority. The purpose of this study was to identify the South Carolina counties with the greatest risk for ECC. As policy-makers seek to address inequities stemming from early childhood caries, documenting its prevalence is essential. METHODS: Since no county level ECC rates were published for South Carolina, we identified an opportunity to strengthen ECC surveillance through public use data, so as to properly equip policy-makers and pediatric providers with an evidence based understanding of the scope of the problem. As a result we sought to develop an overall county level prevalence measure for ECC risk through an ecological analysis of public use data. RESULTS: Ten counties with the greatest overall risk for ECC were all rural as hypothesized. Additionally, seven of the 10 highest risk counties fell into what is often referred to as the "Corridor of Shame." CONCLUSIONS: We have found an affordable way of measuring county level risk for ECC that allows pediatric advocates and policy-makers to develop population level interventions to reduce and measure risk with public-use data.